The role of fibroblast growth factor and epidermal growth factor in the proliferative response of the corneal and lens epithelium

Abstract

Bovine corneal epithelial and lens epithelial cell culture have been developed to study the factors controlling corneal epithelial and lens epithelial cell proliferation. The ultrastructure of bovine corneal and lens epithelial cells grown in vitro was typical of that reported for corneal epithelial cells and lens epithelial cells in vivo. The outstanding structural features of these cells were the various forms of microfilament associations; microtubules were also present, but they were much less numerous and not often associated with each other. Microfilaments did exist in numerous closely-packed filaments. In many instances the microfilaments appear to be associated with junctional complexes (desmosomes) present between adjacent cells. When the mitogenic effect of EGF and FGF was compared on cultures of corneal epithelial cells and lens epithelial cells, FGF increased the labelling index of quiescent cultures of corneal and lens epithelium to a degree comparable to that of serum while EGF had no effect. When the effect of EGF and FGF was compared on the rate of proliferation of sparse cell culture, FGF induced an increase in cell number with corneal epithelial cell culture at 1 ng/ml and its effect was optimal at 10 ng/ml. With lens epithelial cell culture FGF had an effect at concentrations as low as 10 −2 ng/ml and the response leveled off at 100 ng/ml. EGF did not have any effect on the proliferation of corneal or lens epithelial cells from 10 −3 to 10 3 ng/ml although specific EGF binding sites were detected with corneal and lens epithelial cells. The lack of mitogenic effect of EGF on corneal epithelial cell culture stands in contrast to its marked hyperplastic effect (shared by FGF) on epithelium of cornea maintained in organ culture. In contrast to that of FGF, a typical EGF response of the corneal epithelium occurred with combined corneal epithelium and mesenchyme (stroma), but not with epithelium alone. The mitogenic response of a given tissue, such as the cornea, to EGF will then not only depend on the presence of the mitogenic agent or on the sensitivity of the tissue to a mitogenic stimulus at a given time, but will also depend on the topological relationship between tissues from different embryonic origin within the same organ.